Article

Grapes(Chk1) prevents nuclear CDK1 activation by delaying cyclin B nuclear accumulation

Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 11/2008; 183(1):63-75. DOI: 10.1083/jcb.200801153
Source: PubMed

ABSTRACT Entry into mitosis is characterized by a dramatic remodeling of nuclear and cytoplasmic compartments. These changes are driven by cyclin-dependent kinase 1 (CDK1) activity, yet how cytoplasmic and nuclear CDK1 activities are coordinated is unclear. We injected cyclin B (CycB) into Drosophila melanogaster embryos during interphase of syncytial cycles and monitored effects on cytoplasmic and nuclear mitotic events. In untreated embryos or embryos arrested in interphase with a protein synthesis inhibitor, injection of CycB accelerates nuclear envelope breakdown and mitotic remodeling of the cytoskeleton. Upon activation of the Grapes(checkpoint kinase 1) (Grp(Chk1))-dependent S-phase checkpoint, increased levels of CycB drives cytoplasmic but not nuclear mitotic events. Grp(Chk1) prevents nuclear CDK1 activation by delaying CycB nuclear accumulation through Wee1-dependent and independent mechanisms.

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    • "It has been shown that human Chk1 kinase localizes to centrosomes in the interphase and the centrosomeassociated Chk1 prevents premature activation of cyclin B-Cdk1 kinase, which contributes to the proper timing of the initiation of mitosis (Kramer et al., 2004). In Drosophila, Grp (Chk1) prevents nuclear cyclin-dependent kinase 1 (Cdk1) activation by delaying cyclin B nuclear accumulation (Royou et al., 2008). Interestingly, Chk1 is a Cdk target, Chk1 can be phosphorylated at serine 286 and serine 301 by Cdk1 during mitosis, the mitotic phosphorylation of Chk1 promotes the translocation of Chk1 from the nucleus to the cytoplasm in prophase, thus releasing an inhibitory effect of Chk1 on Cdk1 to promote mitotic entry (Enomoto et al., 2009). "
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    Life sciences 04/2014; DOI:10.1016/j.lfs.2014.04.011 · 2.30 Impact Factor
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    • "Another study revealed that mutations that increased CycB levels in early interphase 14 caused a successful, early mitosis (Papoulas et al. 2010) that we interpret as indicative of a shortened S phase. Moreover, there is a 5-min window at the beginning of interphase 14, when injections of stable CycB protein can drive embryos into an early mitosis (Royou et al. 2008). The success of the mitosis was not assayed due to interference from the stable cyclin, but S phase was probably shortened, given the previously cited result. "
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    Genes & development 03/2012; 26(7):714-25. DOI:10.1101/gad.186429.111 · 12.64 Impact Factor
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    • "The molecular nature of the N:C signal remains elusive, but ultimately impacts Cyclin-dependent kinase 1 (CDK1, also known as CDC2) through multiple mechanisms. These include modulation of Cyclin B (CYCB) levels through rounds of protein synthesis and degradation (Edgar et al., 1994; Huang and Raff, 1999; Raff et al., 2002), activation of the grp (Chk1) and mei-41 (atr) DNA damage checkpoint pathway (Fogarty et al., 1997; Sibon et al., 1997; Sibon et al., 1999; Royou et al., 2008), and precisely timed zygotic transcription of the mitotic cyclin-dependent kinase (M-CDK1) inhibitors frühstart (frs; Z600 – FlyBase) and tribbles (trbl) (Grosshans and Wieschaus, 2000; Mata et al., 2000; Grosshans et al., 2003; Gawlinski et al., 2007). It is clear that degradation of maternal mRNA and initiation of zygotic transcription contribute to the timing and morphological events of the MBT (Arbeitman et al., 2002; Tadros and Lipshitz, 2005; Pilot et al., 2006; De Renzis et al., 2007; Lu et al., 2009; Tadros and Lipshitz, 2009); however, the translational regulatory mechanisms that modulate rates of protein synthesis during this transition are largely unexplored. "
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